tbuckley/cabot-search huggingface dataset:
Effect of COVID-19 vaccination and booster on maternal–fetal outcomes: a retrospective cohort study
Authors: Samantha N Piekos, Yeon Mi Hwang, Ryan T Roper, Tanya Sorensen, Nathan D Price, Leroy Hood, Jennifer J Hadlock
Journal: The Lancet Digital Health (2023)

COVID-19 in pregnant people increases the risk for poor maternal-fetal outcomes. However, COVID-19 vaccination hesitancy remains due to concerns over the vaccine's potential effects on maternal-fetal outcomes. Here we examine the impact of COVID-19 vaccination and boosters on maternal SARS-CoV-2 infections and birth outcomes.
Surgical versus non-surgical management for patients with malignant bowel obstruction (S1316): a pragmatic comparative effectiveness trial
Authors: Robert S Krouse, Garnet L Anderson, Kathryn B Arnold, Cynthia A Thomson, Valentine N Nfonsam, Mazin F Al-Kasspooles, Joan L Walker, Virginia Sun, Angeles Alvarez Secord, Ernest S Han, Alberto M Leon-Takahashi, David Isla-Ortiz, Phillip Rodgers, Samantha Hendren, Marco Sanchez Salcedo, Jonathan A Laryea, Whitney S Graybill, Devin C Flaherty, Harveshp Mogal, Thomas J Miner, Jose M Pimiento, Mio Kitano, Brian Badgwell, Giles Whalen, Jeffrey P Lamont, Oscar A Guevara, Maheswari S Senthil, Summer B Dewdney, Eric Silberfein, Jason D Wright, Bret Friday, Bridget Fahy, Sandeep Anantha Sathyanarayana, Mark O'Rourke, Marie Bakitas, Jeff Sloan, Marcia Grant, Gary B Deutsch, Jeremiah L Deneve
Journal: The Lancet. Gastroenterology & hepatology (2023)
Corrigendum to: USP36 promotes tumorigenesis and drug sensitivity of glioblastoma by deubiquitinating and stabilizing ALKBH5
Journal: Neuro-Oncology (2023)

Additional criteria apply.Please refer to protocol 14379-201 for full inclusion and exclusion criteria.† Patients can participate if they had some skin cancers, superficial bladder cancer (cancer that was only on the surface of the lining of the bladder), or carcinoma in situ (cancer that had not spread) of the cervix or breast that had been cured.HIV, human immunodeficiency virus; HBV, hepatitis B virus; HCV, hepatitis C virus; IGF-1R, insulin-like growth factor 1 receptor; KPS, Karnofsky Performance Scale; RT, radiotherapy; SOC, standard of care; TMZ, temozolomide.
p55γ degrades RIP3 via MG53 to suppress ischaemia-induced myocardial necroptosis and mediates cardioprotection of preconditioning
Authors: Zhenyan Li, Rilei Dai, Min Chen, Lixuan Huang, Kun Zhu, Mingyang Li, Wenting Zhu, Yang Li, Ning Xie, Jingchen Li, Li Wang, Feng Lan, Chun-Mei Cao
Journal: Cardiovascular Research (2023)

Regulated necrosis (necroptosis) and apoptosis are important biological features of myocardial infarction, ischaemia-reperfusion (I/R) injury, and heart failure. However, the molecular mechanisms underlying myocardial necroptosis remain elusive. Ischaemic preconditioning (IPC) is the most powerful intrinsic cardioprotection against myocardial I/R injury. In this study, we aimed to determine whether IPC suppresses I/R-induced necroptosis and the underlying molecular mechanisms.
XPO1 inhibition sensitises CLL cells to NK cell mediated cytotoxicity and overcomes HLA-E expression
Authors: Jack G. Fisher, Amber D. P. Doyle, Lara V. Graham, Shreyanshi Sonar, Ben Sale, Isla Henderson, Luis Del Rio, Peter W. M. Johnson, Yosef Landesman, Mark S. Cragg, Francesco Forconi, Christopher J. Walker, Salim. I. Khakoo, Matthew D. Blunt
Journal: Leukemia (2023)

Abstract The first-in-class inhibitor of exportin-1 (XPO1) selinexor is currently under clinical investigation in combination with the BTK inhibitor ibrutinib for patients with chronic lymphocytic leukaemia (CLL) or non-Hodgkin lymphoma. Selinexor induces apoptosis of tumour cells through nuclear retention of tumour suppressor proteins and has also recently been described to modulate natural killer (NK) cell and T cell cytotoxicity against lymphoma cells. Here, we demonstrate that XPO1 inhibition enhances NK cell effector function against primary CLL cells via downregulation of HLA-E and upregulation of TRAIL death receptors DR4 and DR5. Furthermore, selinexor potentiates NK cell activation against CLL cells in combination with several approved treatments; acalabrutinib, rituximab and obinutuzumab. We further demonstrate that lymph node associated signals (IL-4 + CD40L) inhibit NK cell activation against CLL cells via upregulation of HLA-E, and that inhibition of XPO1 can overcome this protective effect. These findings allow for the design of more efficacious combination strategies to harness NK cell effector functions against CLL.
Prospective Screening for Transthyretin Cardiac Amyloidosis in Spinal Stenosis Surgery Patients
Authors: Philippe Debonnaire, Mathias Claeys, Pascale De Paepe, Emma Christiaen, Bert Geerts, Frank De Geeter, Sander Trenson, Davy Hoste, Jan Van Droogenbroeck, Kristof Verhoeven, Nikolaas Vantomme, René Tavernier
Journal: JACC CardioOncology (2023)
The Complex Patchwork of Transportation for In-Center Hemodialysis
Authors: Frances F. Tian, Yoshio N. Hall, Sauntia Griffin, Torie Kranze, Debra Marcella, Suzanne Watnick, Ann M. O'Hare
Journal: Journal of the American Society of Nephrology (2023)

Reliable transportation is an important determinant of access to health care and health outcomes that carries particular significance for people with ESKD. In the United States, there are almost half a million patients receiving treatment with in-center dialysis, translating into more than 70 million roundtrips to dialysis centers annually. Difficulty with transportation can interfere with patients' quality of life and contribute to missed or shortened dialysis treatments, increasing their risk for hospitalization. Medicare, the principal payer for dialysis in this country, has not traditionally provided coverage for nonemergency medical transportation, placing the burden of traveling to and from the dialysis center on patients and families and a range of other private and public entities that were not designed and are poorly equipped for this purpose. Here, we review the relationship between access to reliable transportation and health outcomes such as missed and shortened dialysis treatments, hospitalizations, and quality of life. We also describe current approaches to the delivery of transportation for patients receiving in-center hemodialysis, highlighting potential opportunities for improvement.
Androgen Receptor Variants Confer Castration Resistance in Prostate Cancer by Counteracting Antiandrogen-Induced Ferroptosis
Authors: Rui Sun, Binyuan Yan, Hao Li, Donglin Ding, Liguo Wang, Jun Pang, Dingwei Ye, Haojie Huang
Journal: Cancer Research (2023)

Abstract Androgen receptor (AR) inhibition by androgen deprivation and/or antiandrogen administration is the mainstay therapy for advanced prostate cancer. However, most prostate cancers ultimately become resistant to these therapies, indicating the importance of identifying mechanisms driving resistance to improve patient outcomes. Here we demonstrated that acute treatment with the antiandrogen enzalutamide (ENZ) decreased glutathione (GSH) production, increased lipid peroxidation, and induced ferroptosis in prostate cancer cells. Consistently, meta-analysis of transcriptomic data linked the androgen-AR axis to metabolism-related biological processes, including lipid metabolism. The cystine transporter gene SLC7A11 was a key AR target, and full-length AR (AR-FL) transactivated SLC7A11 transcription by directly occupying the SLC7A11 promoter and putative enhancer regions. AR variants (AR-V) preferentially bound the SLC7A11 enhancer and upregulated SLC7A11 expression, thereby conferring resistance to ferroptosis induced by ENZ treatment. However, this effect was abolished following downregulation of AR-Vs using the dual CBP/p300 and BET inhibitor NEO2734. These findings reveal ferroptosis induction as an anticancer mechanism of antiandrogens and SLC7A11 as a direct target gene of AR-FL and AR-Vs. AR-V-mediated SLC7A11 expression represents a mechanism coupling ferroptosis resistance to prostate cancer progression. Significance: Upregulation of SLC7A11 can be induced by androgen receptor variants to inhibit antiandrogen-induced prostate cancer cell ferroptosis and to drive castration resistance in prostate cancer.
Regulation of localized corrosion of 316L stainless steel on osteogenic differentiation of bone morrow derived mesenchymal stem cells
Authors: Meng Li, Jing Wu, Wenbo Geng, Yulu Yang, Xuan Li, Kun Xu, Ke Li, Yan Li, Qiaojian Duan, Pengfei Gao, Kaiyong Cai
Journal: Biomaterials (2023)
Authors' Reply: Renal Function and Adverse Maternal and Fetal Outcomes: New Evidence
Authors: Jessica Tangren, Michelle A. Hladunewich
Journal: Journal of the American Society of Nephrology (2023)

We thank you for giving us the opportunity to respond to the Letter to the Editor regarding our recent publication on maternal and fetal outcomes in CKD pregnancies in Ontario.1 The authors, correctly, point out that we only studied the effect of CKD on maternal and fetal pregnancy outcomes but not the effect of pregnancy on CKD progression.2 As practicing obstetric-focused nephrologists, we have a deep appreciation for the role that pregnancy may play in CKD progression and that the current published literature does not adequately quantify this risk. Members of our group (L.B., A.G., and M.H.) have already begun to analyze CKD progression outcomes using updated data from this cohort, so stay tuned. Regarding the letter writers' second concern, we agree that knowing more about GFR changes in pregnancy will enhance our understanding of the interplay between kidney function, placental development, and maternal/fetal outcomes. Because we used real-world data for this study, and serial assessments of kidney function are not part of the standard of care in pregnancy in Canada (or elsewhere in the world), we do not have this information available to analyze. One of our authors (J.T.) is currently studying longitudinal changes in renal filtration markers across pregnancy in two large pregnancy cohorts as part of a National Institutes of Health–funded study on kidney disease in pregnancy. Thank you for reading our paper and taking the time to draw attention to the need for ongoing studies to improve maternal fetal outcomes in our patients with CKD.
SETD2 Loss and ATR Inhibition Synergize to Promote cGAS Signaling and Immunotherapy Response in Renal Cell Carcinoma
Authors: Xian-De Liu, Yan-Ting Zhang, Daniel J. McGrail, Xuesong Zhang, Truong Lam, Anh Hoang, Elshad Hasanov, Ganiraju Manyam, Christine B. Peterson, Haifeng Zhu, Shwetha V. Kumar, Rehan Akbani, Patrick G. Pilie, Nizar M. Tannir, Guang Peng, Eric Jonasch
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Immune checkpoint blockade (ICB) demonstrates durable clinical benefits in a minority of patients with renal cell carcinoma (RCC). We aimed to identify the molecular features that determine the response and develop approaches to enhance it. Experimental Design: We investigated the effects of SET domain-containing protein 2 (SETD2) loss on the DNA damage response pathway, the cytosolic DNA-sensing pathway, the tumor immune microenvironment, and the response to ataxia telangiectasia and rad3-related (ATR) and checkpoint inhibition in RCC. Results: ATR inhibition activated the cyclic GMP–AMP synthase (cGAS)-interferon regulatory factor 3 (IRF3)–dependent cytosolic DNA-sensing pathway, resulting in the concurrent expression of inflammatory cytokines and immune checkpoints. Among the common RCC genotypes, SETD2 loss is associated with preferential ATR activation and sensitizes cells to ATR inhibition. SETD2 knockdown promoted the cytosolic DNA-sensing pathway in response to ATR inhibition. Treatment with the ATR inhibitor VE822 concurrently upregulated immune cell infiltration and immune checkpoint expression in Setd2 knockdown Renca tumors, providing a rationale for ATR inhibition plus ICB combination therapy. Setd2-deficient Renca tumors demonstrated greater vulnerability to ICB monotherapy or combination therapy with VE822 than Setd2-proficient tumors. Moreover, SETD2 mutations were associated with a higher response rate and prolonged overall survival in patients with ICB-treated RCC but not in patients with non–ICB-treated RCC. Conclusions: SETD2 loss and ATR inhibition synergize to promote cGAS signaling and enhance immune cell infiltration, providing a mechanistic rationale for the combination of ATR and checkpoint inhibition in patients with RCC with SETD2 mutations.
Making the Money Follow the Consensus in Nephrology Payment Reform
Authors: Mukta Baweja, Joseph A. Vassalotti
Journal: Journal of the American Society of Nephrology (2023)

1Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York 2National Kidney Foundation, New York, New York Correspondence: Dr. Joseph A. Vassalotti, Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, One Gustave L. Levey Place, Box 1243, New York, NY 10029. Email: [email protected] Published online ahead of print. Publication date available at www.jasn.org See related article, "Optimal Care for Kidney Health: Development of a Merit-based Incentive Payment System (MIPS) Value Pathway," on pages 1315–1328.
Helen Salisbury: Continuing disquiet on the data front
Authors: Helen Salisbury
Journal: BMJ (2023)

People talk to their doctors in confidence, expecting the details they share about their weight, alcohol use, terminations of pregnancy, or thoughts of suicide to remain in the consulting room.They also assume that if they need emergency care in another part of the health system the details of their past operations, current medicines, and allergies will be available to the doctors treating them.Although many patients are happy for their medical information to be used for a wide variety of purposes, other people wish it to be used only for their personal direct care, even if it's anonymised.
Topic modeling identifies novel genetic loci associated with multimorbidities in UK Biobank
Authors: Yidong Zhang, Xilin Jiang, Alexander J. Mentzer, Gil McVean, Gerton Lunter
Journal: Cell Genomics (2023)

Many diseases show patterns of co-occurrence, possibly driven by systemic dysregulation of underlying processes affecting multiple traits. We have developed a method (treeLFA) for identifying such multimorbidities from routine health-care data, which combines topic modeling with an informative prior derived from medical ontology. We apply treeLFA to UK Biobank data and identify a variety of topics representing multimorbidity clusters, including a healthy topic. We find that loci identified using topic weights as traits in a genome-wide association study (GWAS) analysis, which we validated with a range of approaches, only partially overlap with loci from GWASs on constituent single diseases. We also show that treeLFA improves upon existing methods like latent Dirichlet allocation in various ways. Overall, our findings indicate that topic models can characterize multimorbidity patterns and that genetic analysis of these patterns can provide insight into the etiology of complex traits that cannot be determined from the analysis of constituent traits alone.
MANF brakes TLR4 signaling by competitively binding S100A8 with S100A9 to regulate macrophage phenotypes in hepatic fibrosis
Authors: Chao Hou, Dong Wang, Mingxia Zhao, Petek Ballar, Xinru Zhang, Qiong Mei, Wei Wang, Xiang Li, Qiang Sheng, Jun Liu, Chuansheng Wei, Yujun Shen, Yi Yang, Peng Wang, Juntang Shao, Sa Xu, Fuyan Wang, Yang Sun, Yuxian Shen
Journal: Acta Pharmaceutica Sinica B (2023)

The mesencephalic astrocyte-derived neurotrophic factor (MANF) has been recently identified as a neurotrophic factor, but its role in hepatic fibrosis is unknown. Here, we found that MANF was upregulated in the fibrotic liver tissues of the patients with chronic liver diseases and of mice treated with CCl4. MANF deficiency in either hepatocytes or hepatic mono-macrophages, particularly in hepatic mono-macrophages, clearly exacerbated hepatic fibrosis. Myeloid-specific MANF knockout increased the population of hepatic Ly6Chigh macrophages and promoted HSCs activation. Furthermore, MANF-sufficient macrophages (from WT mice) transfusion ameliorated CCl4-induced hepatic fibrosis in myeloid cells-specific MANF knockout (MKO) mice. Mechanistically, MANF interacted with S100A8 to competitively block S100A8/A9 heterodimer formation and inhibited S100A8/A9-mediated TLR4-NF-κB signal activation. Pharmacologically, systemic administration of recombinant human MANF significantly alleviated CCl4-induced hepatic fibrosis in both WT and hepatocytes-specific MANF knockout (HKO) mice. This study reveals a mechanism by which MANF targets S100A8/A9-TLR4 as a "brake" on the upstream of NF-κB pathway, which exerts an impact on macrophage differentiation and shed light on hepatic fibrosis treatment.
Advances in the development of amorphous solid dispersions: The role of polymeric carriers
Authors: Jie Zhang, Minshan Guo, Minqian Luo, Ting Cai
Journal: Asian Journal of Pharmaceutical Sciences (2023)

Amorphous solid dispersion (ASD) is one of the most effective approaches for delivering poorly soluble drugs. In ASDs, polymeric materials serve as the carriers in which the drugs are dispersed at the molecular level. To prepare the solid dispersions, there are many polymers with various physicochemical and thermochemical characteristics available for use in ASD formulations. Polymer selection is of great importance because it influences the stability, solubility and dissolution rates, manufacturing process, and bioavailability of the ASD. This review article provides a comprehensive overview of ASDs from the perspectives of physicochemical characteristics of polymers, formulation designs and preparation methods. Furthermore, considerations of safety and regulatory requirements along with the studies recommended for characterizing and evaluating polymeric carriers are briefly discussed.
Monitoring, prophylaxis, and treatment of infections in patients with MM receiving bispecific antibody therapy: consensus recommendations from an expert panel
Authors: Noopur Raje, Kenneth Anderson, Hermann Einsele, Yvonne Efebera, Francesca Gay, Sarah P. Hammond, Alexander M. Lesokhin, Sagar Lonial, Heinz Ludwig, Philippe Moreau, Krina Patel, Karthik Ramasamy, Maria-Victoria Mateos
Journal: Blood Cancer Journal (2023)

Abstract Bispecific antibodies (BsAbs) are emerging as an important novel class of immunotherapeutic agents for the treatment of multiple myeloma (MM), and are set to be more widely used in clinical practice. However, this new class of therapies is associated with a distinct adverse event (AE) profile that includes cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, as well as AEs leading to increased infection risk such as cytopenias and hypogammaglobulinemia, and infections themselves. As preliminary data with this class of agents shows an increased risk of infections as compared with conventional MM treatment regimens, such as immunomodulatory drugs, proteasome inhibitors, and anti-CD38 monoclonal antibodies (mAbs), guidance on infection monitoring, prophylaxis and treatment is required. This review provides consensus recommendations from a panel of 13 global experts, following a meeting in August 2022. The meeting objective was to review existing literature and identify relevant information on infections with all BsAbs in patients with MM, as well as to discuss clinical experience of experts in managing these infections. The recommendations outlined here can be used to guide management of infection risk factors, such as hypogammaglobulinemia and neutropenia. In addition, they can be used to guide the monitoring, prophylaxis, and treatment of bacterial, viral and fungal infections, including emerging infections of interest, such as coronavirus 2019 (COVID-19), and the use of vaccinations prior to and during BsAb treatment. The recommendations have been graded by the panel based on level of data available. Key recommendations include universal herpes simplex and varicella zoster virus prophylaxis, screening for hepatitis B virus reactivation risk in all patients, monthly intravenous immunoglobulin treatment for immunoparesis and in the absence of life-threatening infectious manifestations, use of colony-stimulating factors in patients with Grade 3 neutropenia, universal pneumocystis jirovecii pneumonia prophylaxis and no routine anti-fungal prophylaxis.
Association of histopathologic grade with stage and survival in sebaceous carcinoma: A retrospective cohort study in the National Cancer Database
Authors: Nolan J. Maloney, Natasha C. Zacher, Sumaira Z. Aasi, Kelsey E. Hirotsu, Lisa C. Zaba, Nour Kibbi
Journal: Journal of the American Academy of Dermatology (2023)

Five hundred ten women identified as SMW (lesbian [20.4%], bisexual [66.9%], something else [12.7%]) and 6378 as heterosexual (response rate to SPB questionnaire: 92.3% [6359/6888]).Compared to heterosexual women, SMW were less likely to use sunscreen (aOR 0.77, 95% CI 0.61-0.99),but reported similar long-sleeve clothing use and shade-seeking.SMW spent more time outdoors on workdays (difference 29.1 minutes, 95% CI 19.4-38.9)and nonworkdays (difference 24.7 minutes, 95% CI 13.8-35.6).SMW also had an increased odds of spending at least 3 hours outdoors during workdays (aOR 1.95, 95% CI 1.49-2.55)and non-workdays (aOR 1.38, 95% CI 1.12-1.69).SMW were less likely to use sunscreen, suggesting need for targeted SPB education and for future qualitative research exploring reasons underlying differences in sunscreen use in diverse groups of women.Additionally, we demonstrated that SMW spent more time outdoors during the peak hours of sun exposure between 9AM and 5PM on workdays and non-workdays.Differences in occupation related to sexual orientation, including increased SMW concentration in construction and protective services, may be contributing factors. 5Study strengths included use of nationally representative data with high survey response rates.
Type 2 chronic inflammatory diseases: targets, therapies and unmet needs
Authors: Pavel Kolkhir, Cezmi A. Akdis, Mübeccel Akdis, Claus Bachert, Thomas Bieber, Giorgio Walter Canonica, Emma Guttman-Yassky, Martin Metz, Joaquim Mullol, Oscar Palomares, Harald Renz, Sonja Ständer, Torsten Zuberbier, Marcus Maurer
Journal: Nature Reviews Drug Discovery (2023)